HepatitisBisasmallDNAvirusthatcontainsonly4openreADIngframesinitsgenome.ThreeoftheseORFshavebeenidentifiedastheenvelope,capsidandpolymerasegenes,whilethefunctionofthefourthhasremainedunknownuntilrecently.ThefourthreadingframehasbeencalledtheXgeneandproducesHBxproteinthatisessentialforviralreplicationinlivercellsandactsbroadlytoactivateavarietyoftranscriptionfactors.OnehypothesisofHBxactivityhasbeenthatitentersthenucleustoactasatranscriptionalregulator.OnepieceofevidencesupportingthismechanismofHBxactionisthatHBxinteractswiththetranscriptionfactorCREBandincreasesitsDNA-bindingactivity.ThismechanismdoesnotexplainalloftheeffectsofHBxhowever.AnotherhypothesisfortheHBxmechanismofactionisthatHBxincreasescalciumreleaseintothecytoplasm.ThismechanismofactionisconsistentwiththevarietyoftranscriptionfactorsandkinasesaffectedbyHBxsincecalciumsignalingaffectsmanydifferentsignalingpathways.HBxdoesnotappeartointeractdirectlywithRasorproteinkinasesbutdoesappeartoactivatethecalciumactivateproteinkinasePyk2.AdominantnegativeformofPyk2blocksHBxactivityandtheinvolvementofcalciuminHBxactivationofPyk2isindicatedbytheactionofseveralMolecularprobesthataltercytosoliccalciumsignaling.BAPTA-AMchelatescytosolicandblocksHBxaction.CyclosporinAblocksmitochondrialcalciumsignalingandalsoblockedHBxsignaling.CGP37157isacompoundthatblocksthemitochondrialsodiumcalciumpumpandalsoblockshepatitisBviralreplication,indicatingthatmitochondrialcalciumsignalingisthetargetofHBxfunction.Compoundsthatelevatecytoplasmiccalciumlevels(valinomycinandthapsigargin)increasetherateofreplicationofvirusesthatlackHBx,furthersupportingtheroleofHBxasaninducerofintracellularcalciumsignaling.ThemechanismbywhichHBxcausescalciumreleaseisnotyetknown.SrcactivationappearstoinduceviralreplicationwhileRassignalingdoesnot,suggestingthattheactivationofRassignalingbyHBxmayplayadistinctfunction,perhapstheinductionofcancer.

Contributor:GlennCrostonPh.D.

REFERENCES:BouchardMJ,Wang,LH,andSchneider,RJ.CalciumsignalingbyHBxproteininhepatitisBvirusDNAreplication.Science,vol294(5550),2001,2376-8.Ganem,D.(2001)TheXfiles--onestepclosertoclosure.Science294(5550),2299-300Klein,N.P.etal.(1999)SrckinasesinvolvedinhepatitisBvirusreplication.EMBO.J.18(18),5019-27Klein,N.P.,Schneider,R.J.(1997)ActivationofSrcfamilykinasesbyhepatitisBvirusHBxproteinandcoupledsignalingtoRas.Mol.Cell.Biol.17(11),6427-36Williams,J.S.,Andrisani,O.M.(1995)ThehepatitisBvirusXproteintargetsthebasicregion-leucinezipperdomainofCREB.ProcNatlAcadSciUSA92(9),3819-23

================  蚂蚁淘在线  ================

免责声明：本文仅代表作者个人观点，与本网无关。其创作性以及文中陈述文字和内容未经本站证实，对本文以及其中全部或者部分内容、文字的真实性、完整性、及时性本站不做任何保证或承诺，请读者仅作参考，并请自行核实相关内容

版权声明：未经蚂蚁淘在线授权不得转载、摘编或利用其他方式使用上述作品。已经经本网授权使用作品的，应该授权范围内使用，并注明“来源：蚂蚁淘在线”。违反上述声明者，本网将追究其相关法律责任。